Atara Biotherapeutics Announces Collaborator Presentation of Positive Phase 1 Clinical Results for a Mesothelin-Targeted CAR T Immunotherapy in Patients with Advanced Mesothelioma
Best overall response rate for a subset of 11 malignant pleural mesothelioma patients with minimum follow-up time of 3 months who also received pembrolizumab and lymphodepleting chemotherapy was 72% including 2 durable complete metabolic responses and 6 partial responses
Clinical findings presented in Advances in Novel Immunotherapeutics oral session at the
“Clinical results presented by our MSK collaborators reaffirm mesothelin as a promising target for patients with advanced mesothelioma and establish an important proof-of-concept advance for CAR T immunotherapy in solid tumors,” said
The Phase 1 clinical study recruited 21 patients, 19 with malignant pleural mesothelioma (MPM), one with metastatic lung cancer and one with metastatic breast cancer, who received a median of 3 prior treatment regimens, to evaluate the safety and potential anti-tumor activity of a CD28-costimulated, mesothelin-targeted autologous CAR T immunotherapy. The study included six dose cohorts with administration directly to the tumor site using regional delivery techniques, initially at a low CAR T dose without lymphodepleting chemotherapy, followed by increasing CAR T dose cohorts with lymphodepletion. A subset of these patients was subsequently treated with pembrolizumab, a PD-1 checkpoint inhibitor.
Mesothelin-targeted, autologous CAR T administration was found to be generally well-tolerated with no CAR T-related toxicities higher than grade 2 observed based on monitoring multiple clinical, radiological, and laboratory parameters. CAR T cells were found to be persistent in the peripheral blood for 13 of the 21 patients during the 38-week evaluation, and their presence was associated with evidence of tumor regression on imaging studies.
Best overall response rate (ORR) for a subset of 11 MPM patients with minimum follow-up time of 3 months who also received pembrolizumab and lymphodepleting chemotherapy was 72% including 2 durable complete metabolic responses (CMR) on PET imaging and 6 partial responses (PR). Six of the 11 patients in this subset were programmed cell death ligand 1 (PD-L1) negative, defined as undetectable expression of PD-L1 in tumor cells by immunohistochemistry, with 4 of the 8 total responses observed in PD-L1 negative patients (1 CMR and 3 PR).
Following progression on standard platinum-containing chemotherapy, the expected ORR for patients with MPM treated with a checkpoint inhibitor is estimated between 5%-29% with one patient achieving a CR across multiple studies.1-5
MSK is also investigating mesothelin-targeted CAR T cells for patients with mesothelin-associated advanced breast cancer (NCT02792114). Additional results from these ongoing studies are expected to be presented at upcoming scientific congresses.
Presentation CT036: A Phase I clinical trial of malignant pleural disease treated with regionally delivered autologous mesothelin-targeted CAR T cells: Safety and efficacy
Session CTMS01: Advances in Novel Immunotherapeutics
Presentation Date and Time:
1Vogelzang NJ, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003 Jul 15;21(14):2636-44.
2Maio M, et al. Tremelimumab as second-line or third-line treatment in relapsed malignant mesothelioma (DETERMINE): a multicentre, international, randomised, double-blind, placebo-controlled phase 2b trial. Lancet Oncol. 2017 Sep;18(9):1261-1273.
3Scherpereel A, et al. Nivolumab or nivolumab plus ipilimumab in patients with relapsed malignant pleural mesothelioma (IFCT-1501 MAPS2): a multicentre, open-label, randomised, non-comparative, phase 2 trial. Lancet Oncol. 2019 Feb;20(2):239-253.
4Alley EW, et al. Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial. Lancet Oncol. 2017 May;18(5):623-630.
5Hassan R, et al. Avelumab in patients with previously treated mesothelioma: Updated phase 1b results from the JAVELIN Solid Tumor trial. Abstract 166,
This press release contains or may imply "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. For example, forward-looking statements include statements regarding: the applicability of results of MSK’s Phase 1 study to programs being developed by Atara; the status of mesothelin as a promising immunotherapy target; Atara’s ability to develop a next-generation, mesothelin-targeted CAR T immunotherapy using MSK’s novel 1XX CAR signaling domain and PD-1 DNR checkpoint inhibition technologies for patients with mesothelin-associated solid tumors. Because such statements deal with future events and are based on
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Source: Atara Biotherapeutics, Inc.